DESCRIPTION: The long range objectives of the research proposed in this application are to understand the catalytic mechanisms of several enzymes by using advanced electron paramagnetic resonance (EPR) spectroscopic methods to probe the detailed electronic structure of their catalytic sites and to gain an understanding of how these systems control chemical reactivity. The enzymes to be studied are copper-containing amine oxidases, methylamine dehydrogenases, methylmalonyl Coenzyme A Mutase, and carbonmonoxide dehydrogenase. All of these proteins catalyze reactions that involve paramagnetic intermediate states at some point during their cycle. This work will involve further development and use of pulsed and double resonance EPR experiments to measure magnetic and electronic interactions between the unpaired electron spin of the transient paramagnetic species and the magnetic nuclei that comprise their environment. Such hyperfine couplings provide a direct measurement of the highest occupied molecular orbital of the paramagnetic center and thus yield information on the valence electron distribution that is involved in catalysis. Such information is difficult or impossible to obtain by other spectroscopic methods and by X-ray crystallography. Such information will be correlated with the results of kinetic and other structural measurements. In particular the results will be related to electron transferring oxidation/reduction processes.